Syntheses, in vitro α-amylase and α-glucosidase dual inhibitory activities of 4-amino-1,2,4-triazole derivatives their molecular docking and kinetic studies

Yeye, Emmanuel Oloruntoba; Kanwal,; Khan, Khalid Mohammed; Chigurupati, Sridevi; Wadood, Abdul; Rehman, Ashfaq Ur; Perveen, Shahnaz; Maharajan, Mari Kannan; Shamim, Shahbaz; Hameed, Shehryar; Aboaba, Sherifat A.; Taha, Muhammad

doi:10.1016/j.bmc.2020.115467

Cited by 48 publications

(22 citation statements)

References 28 publications

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“…Screening of all the derivatives showed good α‐amylase inhibitory activity with IC 50 =2.01±0.03–6.44±0.16 μM while acarbose showed 1.92±0.17 μM. Indole substituted derivative was the most potent one [69] …”

Section: Synthetic Developments On N‐heterocyclic Compoundsmentioning

confidence: 94%

“…Methyl substituted triazoles with R 3 = 3,4-dichloro showed maximum inhibition potential. [68,69] Rahim et al (2019) introduced triazin indole motifs with more aromaticity by including thiazole/oxazole groups. As shown in scheme 23 isatin 69 gave compound 70 by reacting with thiosemicarbazide in presence of K 2 CO 3 in distilled H 2 O.…”

Section: Five or Six Membered Unsaturated Ring Containing Three Nitro...mentioning

confidence: 99%

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Recent Developments in the Synthesis of N‐Heterocyclic Compounds as α‐Amylase Inhibitors via In‐Vitro and In‐Silico Analysis: Future Drugs for Treating Diabetes

et al. 2022

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In nature, N‐heterocyclic compounds and their derivatives are abundant. They serve as the building blocks of many biological entities, such as enzymes, alkaloids, hormones, antibiotics, and vitamins. The treatment of diabetes is one of the major applications of heterocyclic compounds. Natural as well as synthetic, both types of heterocyclic compounds show anti‐diabetic activity. There is a plethora of literature on the hyper/hypoglycaemic activity of natural compounds. This review discusses the synthesis methods, yields of the reactions and Inhibitory concentration (IC50) values of all the synthesized derivatives via different assays such as 3,5‐dinitrosalicylic acid (DNS) or starch assays. IC50 values of all the derivatives have been compared with those of standard acarbose. Structure activity relationship of most potential compounds with α‐amylase enzyme is established to show the type of interactions between them. Molecular docking studies show the type of interaction between compounds and enzyme.

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Section: Synthetic Developments On N‐heterocyclic Compoundsmentioning

confidence: 94%

Section: Five or Six Membered Unsaturated Ring Containing Three Nitro...mentioning

confidence: 99%

Recent Developments in the Synthesis of N‐Heterocyclic Compounds as α‐Amylase Inhibitors via In‐Vitro and In‐Silico Analysis: Future Drugs for Treating Diabetes

et al. 2022

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“…These enzyme inhibitors prevent various disorders by suppressing an enzyme's overexpression. Therefore, medicinal chemists pay close attention to the quest for new and potentially helpful enzyme inhibitors [18].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, molecular docking, and biological evaluation of 5‐alkyl(aryl)‐2‐isobutylthiazole derivatives: As α‐amylase, α‐glucosidase, and protein kinase inhibitors

Khan

Buğday

Rehman

et al. 2022

Applied Organom Chemis

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A series of 18 biologically active C5‐arylated‐2‐isobutylthiazole derivatives that were synthesized by Pd‐NHC complexes [Pd(μ‐Cl)Cl (NHC)]2, NHC = SIXyl, 2), (LCl2Pd‐NHC, L = PPh3, 3), (LCl2Pd‐NHC, L = Py, 4), (LCl2Pd‐NHC, L = 3‐CHO‐Py, 5) catalyzed C‐H bond activation reactions. The catalytic activity of Pd‐NHC complexes was examined on the C‐H bond activation reaction of 2‐isobutylthiazole. All Pd‐NHC complexes were characterized by 1H nuclear magnetic resonance specroscopy (NMR), 13C NMR, fouirer transform infrared spektroscopy (FTIR), quadrupole‐time of flying‐liquit cromotagraphy/mass spektroscopy (Q‐TOF‐LC/MS), gas chromatography–mass spectrometry (GCMS), and melting point detection technique. The physicochemical properties, pharmacokinetics, and drug‐likeness were calculated by SwissADME. PkCSM database was used to calculate toxicities profile. All the products (6a–6s) were additionally assessed in vitro for their antidiabetic potential using α‐amylase and α‐glucosidase inhibitory activities. The protein kinase activity was performed to evaluate their anticancer activities. All the compounds possess drug‐like characters as they followed Lipinski's rule of five (RO5). Almost all the compounds showed no to fewer toxicities. In addition, other than the compounds, that is, 6a, 6b, 6c, 6m, 6n, 6p, and 6s, the rest of the compounds showed good α‐glucosidase inhibitory potential (IC50 7.17 ± 0.201 to 74.08 ± 0.244 μg/ml) when compared with acarbose standard (IC50 16.59 ± 0.135 μg/ml). All compounds had moderate to good inhibitory potential against the α‐amylase enzyme, with IC50 values ranging from 12.00 ± 0.289 to 76.15 ± 0.477 μg/ml. Eleven analogs (6e, 6f, 6g, 6h, 6j, 6k, 6l, 6n, 6o, 6p, and 6r) showed good to moderate activity. Seven analogs (6a, 6b, 6c, 6d, 6i, 6m, and 6s) showed no α‐amylase inhibitory activity. The protein kinase inhibition potential was determined for the first time, and the compounds 6d, 6e, 6f, 6h, 6k, 6p, and 6r depicted activity with the zone of inhibition in the range of 9 ± 1.3 to 19 ± 1.5 mm. The ligands and active site binding interactions of α‐glucosidase, α‐amylase, and protein kinase enzymes were also studied using molecular modeling.

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“…For instance, the fused 1,2,4-triazole-imidazolidines possess the enhanced anti-proliferative, and HDAC-tubulin inhibitor [22], isonicotinic acid tethered phenacyl triazoles show anticonvulsant [23], S,N-bis(acyclonucleoside) derivatives exhibit anti-tubercular [24], Cox-2 inhibitor [25], properties. Coumarin tethered pyrazole-oxadiazole hybrids show improved antimicrobial and antioxidant activities [26], for instance, Naproxen analogs of 1,2,4-triazole-5-thiones show potential antinociceptive and anti-inflammatory [27], triazolo [4,3-b] [1,2,4] triazepine-8(9H)-ones have α-amylase and α-glucosidase inhibitory [28], and 4-amino-1,2,4-triazole-Schiff's bases exhibit good anti-diabetic [29], activities. In this context, this current study presents the synthesis of coumarin-triazole hybrids, in vitro screening of their anti-diabetic activity, in silico docking and ADME screening studies.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

Basappa

Vivek²,

Kumara

et al. 2020

Heliyon

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The current study demonstrates the synthesis of coumarin-triazole hybrids 8 (a-e) in four steps starting from substituted salicylaldehyde 1 (a-e), and diethyl malonate 2. The spectroscopic studies provide the structure proofs of the new compounds, and the molecular structure of an intermediate 3a by crystallographic studies. The crystal structure analysis revealed the C-H...O, C-H... π, CO ...π and π...π molecular interactions. Further, the intermolecular interactions were quantified using Hirshfeld surface analysis and the DFT method B3LYP functional with 6-311þþ G (d,p) basis set was employed to optimize the molecular geometry. The synthesized new coumarintriazole hybrids, 8 (a-e) were screened for their α-amylase inhibitory potentials, and the results suggest that amongst the series, compounds 8c, and 8e show the promising inhibition of the enzyme, and might act as lead molecules for anti-diabetic activities. To understand the mode of action in silico molecular docking and ADME screening were performed.

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Syntheses, in vitro α-amylase and α-glucosidase dual inhibitory activities of 4-amino-1,2,4-triazole derivatives their molecular docking and kinetic studies

Cited by 48 publications

References 28 publications

Recent Developments in the Synthesis of N‐Heterocyclic Compounds as α‐Amylase Inhibitors via In‐Vitro and In‐Silico Analysis: Future Drugs for Treating Diabetes

Recent Developments in the Synthesis of N‐Heterocyclic Compounds as α‐Amylase Inhibitors via In‐Vitro and In‐Silico Analysis: Future Drugs for Treating Diabetes

Synthesis, molecular docking, and biological evaluation of 5‐alkyl(aryl)‐2‐isobutylthiazole derivatives: As α‐amylase, α‐glucosidase, and protein kinase inhibitors

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

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